Abstract
The bioavailability of trazodone, a new antidepressant, from 50 mg dividose (A) or film-sealed (B) tablets relative to an oral solution was determined in six healthy male subjects using 50 mg of D4-trazodone as a stable isotope labelled standard. Concentrations of trazodone and D4-trazodone were measured by GCMS. The pharmacokinetics of trazodone and D4-trazodone were identical indicating no isotope effect. For formulation A, B and solution, the relative (trazodone/D4-trazodone) Cmax values were 0.84 +/- 0.09, 0.90 +/- 0.05 and 1.05 +/- 0.04. The relative bioequivalence of the dosage formed with a power of 85% (power by conventional ANOVA was 54%). Among subjects % relative standard deviations (RSD) for the D4-trazodone AUC values, a measure of intra-subject variability, were 6 to 38% while the % RSDs by period, a measure of inter-subject variability, were 26 to 55%.
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Selected References
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- Ankier S. I., Martin B. K., Rogers M. S., Carpenter P. K., Graham C. Trazodone--a new assay procedure and some pharmacokinetic parameters. Br J Clin Pharmacol. 1981 May;11(5):505–509. doi: 10.1111/j.1365-2125.1981.tb01157.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baiocchi L., Frigerio A., Giannangeli M., Palazzo G. Basic metabolites of trazodone in humans. Arzneimittelforschung. 1974 Oct;24(10):1699–1706. [PubMed] [Google Scholar]
- Brogden R. N., Heel R. C., Speight T. M., Avery G. S. Trazodone: a review of its pharmacological properties and therapeutic use in depression and anxiety. Drugs. 1981 Jun;21(6):401–429. doi: 10.2165/00003495-198121060-00001. [DOI] [PubMed] [Google Scholar]
- Caccia S., Fong M. H., Garattini S., Zanini M. G. Plasma concentrations of trazodone and 1-(3-chlorophenyl)piperazine in man after a single oral dose of trazodone. J Pharm Pharmacol. 1982 Sep;34(9):605–606. doi: 10.1111/j.2042-7158.1982.tb04807.x. [DOI] [PubMed] [Google Scholar]
- Catanese B., Dionisio A., Barillari G., De Martino C. A comparative study of trazodone serum concentrations in patients with normal or impaired renal function. Boll Chim Farm. 1978 Jul;117(7):424–427. [PubMed] [Google Scholar]
- Heck H. A., Buttrill S. E., Jr, Flynn N. W., Dyer R. L., Anbar M., Cairns T., Dighe S., Cabana B. E. Bioavailability of imipramine tablets relative to a stable isotope-labeled internal standard: increasing the power of bioavailability tests. J Pharmacokinet Biopharm. 1979 Jun;7(3):233–248. doi: 10.1007/BF01060015. [DOI] [PubMed] [Google Scholar]
- Jauch R., Kopitar Z., Prox A., Zimmer A. Pharmakokinetik und Stoffwechsel von Trazodone beim Menschen. Arzneimittelforschung. 1976;26(11):2084–2089. [PubMed] [Google Scholar]
- Wallenstein S., Fisher A. C. The analysis of the two-period repeated measurements crossover design with application to clinical trials. Biometrics. 1977 Mar;33(1):261–269. [PubMed] [Google Scholar]
- Westlake W. J. Symmetrical confidence intervals for bioequivalence trials. Biometrics. 1976 Dec;32(4):741–744. [PubMed] [Google Scholar]